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Патент USA US2124295

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2,124,295
PatentedJluly 19, 1938
PATENT OFFICE
' UNITEDIISTAITES
' 5
2,124,295
ALLAN TOIN’ OINTMENT I
Frederick R. Greenbaum, Philadelphia, Pa., as
'
signor to The National Drug Company, Phila
dclphia, Pa; a corporation-of Pennsylvania
November 9,1935.
No Drawing. Application49,033
-Serial No.
‘
‘
.14 Claims. (Cl. 167-63)
In water, ‘allantoin is soluble only to 0.6%, which
is the maximum concentration‘ by this medium.
The object of the invention is primarily to pre
pare a composition comprising allantoin in pro
portions greater'thanthe maximum which is pos
sible in a saturated aqueous solution, and more 4
particularly to prepare such composition in the.
form of an ointment, in which the allantoin is
0
The best concentration reported by William Rob
inson, Ph. D., of the Division of Insects Affecting
Man and Animals, Bureau of Entomology and
Plant Quarantine, United States Department of
Agriculture, Washington, D. C,, was 0.5% in '
when chilled nor deteriorate in high sunlight.
Allantoln is usually obtainable in crystalline
_ By way of explanation, it has long been known
~
form'and
is bland, stable, harmless, odorless and l0
that maggots in infested or infected wounds non-staining.
Heretofore, the most satisfactory
secrete a de?nite substance, which stimulates-the I method of preparation consisted in heating a
uniformly distributed, and will not crystallize
water;
growth of vascular granulations, after removing
‘ cleansing the wound and placing it‘ in a healthy,
condition.
,
k
,
'
‘
The characteristic substance in the allantoic
fluid is allantoin, and the former is a constituent
of the urinary secretions of surgical maggots, or
an end product of purine metabolism, which
arthropods ' like _ most
other animals
secrete
.v
_.
'
'
,
should not-be chilled as in a refrigerator‘, as the
through or from'their intestines, and is directly
‘the result of the, disintegration or' oxidation of
uric acid in an alkaline medium‘, being charac
terized by an alkaline reaction sometimes as high
as pH 8.2,
\
?ask-of water to “near, the boiling point; then
adding the allantoin and gently stirring and heat
ing without boiling until the crystals are dis 15
solved. The solution cannot be autoclaved or
boiled-without a resultant chemical change, and
necrotictissue and reducing infection, thereby
healing
I
'
Fortunately, while the ?rst experiments in the
allantoin easily crystallizesout, while it is also
advisable to keep it away from excessive sunlight. 20
In order to‘obtain higher ‘concentrations than
0.5%, various methods. of combining allantoin
with other substances were tried, including the
possibilities offered by an ointment form.‘ Here
again, various methods of preparation had to be 25’
experimented with, until there was' discovered a
process. whereby any desired concentration can
therapeutic use of allantoin were conducted with . be obtained. .In carrying out this process in its
this substanceobtained from animal secretions, preferred form,‘ approximately 630 grams of
allantoin can now bev obtained'commerclally, be
stearic acid is melted at waterbath temperature, 30
produced by chemical synthesis from uric and
.30 ing
then held at a temperature of substantially
acid. Inv the maggot-infested wounds, as- the ‘70°C. Separately, about 500 cc. of distilled water
amount of allantoin is necessarily low, and is is heated to almost but not quite boiling tempera
further diluted with the serous discharge from
ture. (at sea level), and to this heated water’ .
the wound, it is quite obvious that no great con
approximately"40 grams of allantoin is ‘added and 35
centration
of
the
substance
is
ordinarily
present,
25 but in spite of which fact markedly accelerated stirred until all- of the latter is, in solution.‘ '
To the solution of allantoin, substantially 400
healing‘ has been noted for many years under the
grams of gly'cerine and substantially‘ 20 grams of
fmost adverse 'condltions'as to foreign matter in‘ triethanolamine
are ?nally added. The result
an initial infection of the wound.‘
' .
ing
aqueous,glycerine-triethanolamine
solution of to
ri‘he type of cases in which allantoin treatment allantoin is thenbrought to a temperature
of
has been exceedingly efficacious include chronic’
Pnon-healing wounds with oedematous, indolent
tissues lining the wounds, poor in circulation‘ and
approximately ‘70° 0., and gradually poured with
constant stirring into the melted stearic acid.
' discharging pus; chronicvulcers; extensive burns; ' which has been maintained at substantially 70 °' 0.
Slow stirring is continued until a white, uniform
45 wounds in which the suppuration had already
ointment'ls obtained, after fwhichsumcient addi
been reduced but with little granulation: osteo
myelitis; sloughing ulcers of the leg; prurltus ani
or pruritus vulvae; carbuncles; gangrene; and
, many others 'in which tissue granulation is de
50
sired.
.
.
In many if not all of, these cases, however, it
' was felt that more rapid tissue granulation would
- .55
tional water also at substantially 70° C. is added
to‘ bring the total weight to 2,000 grams; This
provides an ointment in a greaseless base, con
taining. approximately ‘2% allantoin uniformly
distributed and suspended in solution and both‘
in colloidal and crystalline form, or in otlfer
providing a combined colloidal dispersion
be assured, if‘ it were only possible to apply the words,
and minute crystal form of allantoin throughout
allantoin in a higher concentration, than that, the greaseless base. When higher'concentrations
vheretofore available in‘ the form of a solution.
2
2,124,295
are desired, a greater amount, in fact, much vtoin, 400 grams of glycerine, 60 grams of tri
- larger amounts of allantoin may be dissolved in
the. boiling water, practically any desired per
centage of allantoin in the ointment being pos
sible.
.
-
-
T
'
From the proportions of triethanolamine and
stearic acid used it will be apparent from their
molecular weights of 284 and 140, respectively,
that these substances will combine to produce tri
~10 ethanolamine-stearate and an excess of s'tearic
acid in the ‘?nal. ointment. Such an excess of
acid is a de?nite prerequisite-of a highly success:
ful ointment of the type produced by the appli
cant, as such an excess-‘insures. a permanently
acid condition, and thereby prevents a loss of
potency (i. e., healing effect) in the presence of
free' alkaiies. For instance, should an exact
chemical balance of stearic acid and triethanol
amine be used in accordance with their respec
20 tive molecularweights, any water or even the
exudate from the wound would cause an alkaline
reaction, thereby o?setting or nulliiying the ef
' fectiveness' of the product and it is just such a
ethanolamine-stearate, and water, said vallantoin
after cooling .being colloidally dispersed through
out the ointment.
7. An allantoin ointment, containing 590 grams
of excess stearic acid, 400 grams of glycerine,
60 grams of triethanolamine-stearate, water, and
allantoin, said allantoin after cooling being col
loidally dispersed throughout the ointment.‘
8. An allantoin ointment, containing 590 grams
of excess stearic acid, 400 grams of glycerine, 60
grams of triethanolamine-stearate, water, and
sumcient allantoin to provide a speci?c percent
age of concentration, said allantoin after cooling
being colloidally dispersed throughout the oint
ment.
9. The process of preparing a greaseless allan
toin ointment, which consists in melting 630
grams'of stearic acid at water bath temperature
and holding the same at substantially 70° C., .
separately dissolving 40 grams of allantoin crys
tals in 500 cc. distilled water heated to slightly
below the boiling point at sea level, adding 400 '
condition that the excess of acid precludes.
grams of glycerine and 20 grams of triethanol
25
Clinically, the 2% ‘and the 5% allantoin oint- - amine to the allantoin solution, said aqueous
4 ments have been extensively tried, and as was
giycerine-triethanolamine .solution of allantoin
anticipated, the healing results have been i'ound
to be far‘superior to that of the 0.5% or 0.6%
solutions. vIt is believed, furthermore. that in
30 certain types 01'. wounds much higher concentra
tions of allantoin in the ointment form, as above
provided for, will prove proportionately advan
tageous in stimulating the growth of vascular
granulations, removing necrotic tissue and re
35
ducing infection, thereby cleansing the wound and
bringing about a desired healthy condition
requisite to rapid healing. ,
' ‘Having thus described my ‘invention what I
claim‘as‘ new and desire to secure by Letters
Patent is:—
40
.
being raised to a temperature of 70° C., and then
poured with slow and constant stirring into the
melted stearic acid, said stirring being continued
until a white, uniform ointment is obtained, to
provide/ 60 grams of triethanolamine-stearate
and 590 grams excess stearic acid, and to produce
upon cooling minute crystals, a solution and a col
loidal dispersion of. the allantoin throughout the
ointment.
_' A
_
'
v10. The process of preparing a two-percent
allantoin ointment, which consists in melting 630
grams of ‘stearic acid at water bath temperature
and holding the same at substantially 70° 0.,
‘separately dissolving 40 grams ofallantoin crys
' 1. An ointment, containing triethanolamine _ tals in 500 cc. distilled water heated to slightly
stearate, an excess of stearic acid sufficient to
below the boiling point at sea level, adding 400
maintain the ointment acid in reaction, and
grams of glycerine and 20 grams of triethanol- ‘
allantoin particles-asminute as colloids dispersed
45
therein.
.
_
.
2. An ointment, containing triethanolamine
amine to the allantoin solution, said aqueous
glycerine-triethanolamine solution of allantoin
being raised to a temperature of 70° C., and then
stearate, an excess of stearic acid su?lcient to 7 poured with slow and constant stirring into the
maintain the ointment acid in reaction, and more melted stearic acid, said stirring being continued
than "0.6% allantoin colloidally dispersed therein. until a white, uniform ointment is obtained, to
3. An ointment, containing triethanolamine
stearate, anexcess of stearic acid su?lcient to
maintain the ointment acid in reaction,v glycerine
and allantoin colloidally dispersed therein.
.
4. An‘ ointment, containing triethanolamine
55 stearate, an excess of- stearic acid su?icient to
. maintain theointment acidin reaction, glycerine,
and more than 0 6% of allantoin colloidally dis
persed therein.
3
'
,
5. A. two-percent allantoin ointment, contain
60 irg approximately 590 grams 0! excess stearic
acid, 40 grams of allantoin, 400 grams of glycerine,
60 grams 01' triethanolamine-stearate, and water,
saidallantoin after cooling being colloidally dis
persed throughout the ointment.
‘6, A-two-percent to ?ve-percent allantoin oint
ment',..contalning approximately 590 grams of
I; ,,exces__s_ stearic acid, from 40 to 100 grams of allan
provide 60 grams of triethanolamine-stearate
and 590 grams excess stearic acid after which
su?iclent additional water is added- to bring the
total weight to 2000 grams and upon cooling said .
allantoin being in solution, in minute crystals and
colloidally dispersed throughout the mass.
.11. An ointment, comprising the colloidal dis
persion of allantoin in a greaseless base.
12. An ointment, comprising a base, and allan
toin colloidally dispersed throughout said base. .
13'. An ointment, comprising a base throughout
which more than 0.6%. allantoin is dispersed in
the form of a solution and minute particles.
14. An ointment, comprising a base throughout
which allantoin is dispersed in the form of a solu
tion, minute crystals and colloids.
FREDERICK R. GREENBAUM.
ma
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